Authors: Vieira, Marcelo¹; Figueroa-Villar, J.²; Meirelles, M.³; Ferreira, Sérgio¹; Felice, Fernanda⁴

Source: Cell Biochemistry and Biophysics, Volume 44, Number 3, October 2006 , pp. 549-553(5)

Publisher: Humana Press

Abstract:

Protein amyloid aggregation is associated with a number of important human pathologies, but the precise mechanisms underlying the toxicity of amyloid aggregates are still incompletely understood. In this context, drugs capable of blocking or interfering with the aggregation of amyloidogenic proteins should be considered in strategies aimed at the development of novel therapeutic agents. Human lysozyme variants have been shown to form massive amyloid deposits in the livers and kidneys of individuals affected by hereditary systemic amyloidosis. Currently, there are no clinical treatments available to prevent or reverse formation of such amyloid deposits. We have recently described a number of di- and trisubstituted aromatic compounds that block the formation of soluble oligomers and amyloid fibrils of the β-amyloid peptide (Aβ) and protect hippocampal neurons in culture from Aβ-induced toxicity. Here, we show that some of those compounds inhibit the formation and disrupt preformed amyloid fibrils from both human and hen egg white lysozyme. These results suggest that these small molecule compounds may serve as prototypes for the development of drugs for the prevention or treatment of different types of amyloidoses.

Keywords: Protein amyloid aggregation; β-amyloid peptide; hen egg white lysozyme; systemic amyloidosis

Document Type: Research article

DOI: http://dx.doi.org/10.1385/CBB:44:3:549

Affiliations: 1: Instituto de Bioquímica Médica, Programa de Bioquímica e Biofísica Celular, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil, 2: Departamento de Química Orgânica, Instituto Militar de Engenharia, Rio de Janeiro, RJ, Brazil, 3: Departamento de Ultraestrutura e Biologia Celular, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, RJ, Brazil, 4: Instituto de Bioquímica Médica, Programa de Bioquímica e Biofísica Celular, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil, Email: felice@bioqmed.ufrj.br

Publication date: 2006-10-01

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